The development and plasticity of the nervous system involve activity- dependent modification of synaptic connections. We have recently demonstrated that long-term depression (LTD) induced by repetitive synaptic activity at one synapse is accompanied by extensive but selective propagation of the depression to other synapses within the network. The goal of this third year proposal is to further examine the spread of synaptic signals within a neural network. Experiments in Aim 1 are designed to extend the present studies to include synaptic modifications associated with the induction of long-term potentiation (LTP). Experiments in Aim 2 will determine whether the influences from multiple outputs/inputs of a neuron can be spatially and/or temporally integrated. To study the propagation of synaptic modification, we have taken advantage of a very low density primary culture system where groups of three or four hippocampal neurons (triplets or quadruplets) that are connected with one another but relatively isolated from other neurons in the culture can be routinely found. Primarily electrophysiological approaches, using multiple whole-cell recording from defined neural networks, will e used in the proposed studies. This research promises to yield novel information concerning the selective distribution of activity-induced synaptic modification within a simple biological neural network, which has broad implications for understanding the cellular mechanisms underlying the learning processes of the central nervous system.